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The Syilx Okanagan environmental ethic is a philosophy expressed in the practice of Indigeneity as a social (cultural) paradigm and is identified by an inter-reliant experience in the land, as demonstrated in land-use practice which is shaped by the land’s realities as observed, learned and communicated to succeeding generations. Syilx Okanagan Indigeneity reflects an epistemology that optimum human wellbeing cannot be achieved through a human centered ethic but must focus on the optimum ability for the environment to regenerate itself. Syilx Okanagan stories convey the social experience and act as a records system to preserve, maintain and transfer the knowledge of the land. On one level, captikwl contain essential specific environmental knowledge as an oral documentation method, while on another level, as literature, captikwl reconstructs the ethos of interdependency specific to the ecology of the Syilx Okanagan territory through reenactment of nature’s interactions. captikwl in the Nsyilxcen language mimics the dynamic aspects of nature’s required regenerative principles to each succeeding generation, and acts as a feed-back loop reconstructing the social paradigm as an environmental ethic. captikwl might be seen as a distinctly Indigenous human adaptive response scheme within a natural system as it constructs the Syilx Okanagan world and results in behavior with sustainable outcome in the environment. captikwl is a distinct oral artistry that must be read through a literary framework cognizant of oral memory device, structure and Syilx Okanagan context. Okanagan author Morning Dove’s collection of Okanagan stories, as well as, the Mattina and DeSautel bilingual collections and other original version captikwl were consulted. Captikwl demonstrates the concept of tmixw which better translates as a life-force. The word for land is tmxwulaxw, which translates better as a life-force-place, rather than land as location or ecology type. Syilx society demonstrates an “ecological conscience” as the common text through captikwl which is enacted in their social institutions in the manner theorized by respected American conservationist Aldo Leopold, as desirable to achieve within society. The Syilx environmental ethic, rather than a sustainable human ethic of utility, is a willingness to live within a strict imperative to continuously sustain a unity of existence through societal knowledge and reverent practice of respect toward all life-forms. The Syilx environmental ethic diverges from ecocentrism, as articulated by Callicott, in recognizing a fundamental distinction between non-life forms and life forms, in their ability for self-regeneration through inter-reliance, as the focus for delineating moral considerability. The Syilx environmental ethic differs from biocentrism, as articulated by Taylor, in recognizing moral considerability as resting with the on-going life form which is capable of regeneration within its ecology, rather than the singular biological unit. The Syilx environmental ethic also differs from the concept of the ethics of place, as articulated by Berthold-Bond and characterized as an ethical bioregional human utility of a location. Tmixw is the life-force which makes up the tmxwulaxw or life-force-place and the humans are only “placed” as a life-force themselves through Indigeneity as a social paradigm within a criteria of full reciprocity in the regeneration of all life forms of a place. The Syilx environmental ethic also differs from the ethic of sustainability proposed by Daly as a steady state economic model of human utilitarianism, in the positioning of nature treated as capital, to be prudently developed in a way that off-sets depletions of renewable and non-renewable resources in meeting human requirements. The Syilx Okanagan view of economy, while structurally a sustainability model, does not construct value based on human utility as a defining line in decision-making as to which life forms are to be devalued and displaced. Syilx Indigeneity is guided through a societal dialogue practice of Enowkinwixw, a process of decision-making structured to include living within the requirements of the land to fully regenerate. Syilx Okanagan Indigeneity frames an environmental ethic from a tmixwcentric position and offers a model proposing an ethic of re-indigenization as a path to sustainability. The thesis proposes a common text for human society in the form of such literatures, since literature is widely accessible, which demonstrate, imbed and advocate a regenerative land ethic towards the re-indigenization of place.
Transcriptional repression of regulated structural genes in eukaryotes often depends on pleiotropic corepressor complexes. A well-known corepressor conserved from yeast to mammalian systems is Sin3. In addition to Sin3, yeast Cyc8/Tup1 corepressor complex also regulates a diverse set of genes. Both corepressors can be recruited to target genes via interaction with specific DNA-binding proteins, leading to down-regulation of a large number of unrelated structural genes by associated histone deacetylases (HDACs). In vitro interaction studies performed in this work by GST pull-down assays showed that various repressor proteins (such as Whi5, Stb1, Gal80, Rfx1, Ure2, Rdr1, Xbp1, Yhp1, Rox1, Yox1, Dal80 and Mot3) are indeed able to bind pleiotropic corepressors Sin3 and/or Cyc8/Tup1. All repressors interacting with Sin3 contact its paired amphipathic helix domains PAH1 and/or PAH2. Mapping experiments allowed the characterization of minimum repressor domains and to derive a sequence pattern which may be important for repressor interaction with Cyc8 or Sin3. Interactions for some pathway-specific repressors such as Cti6 and Fkh1 have been studied comprehensively; minimal domains of Cti6 and Fkh1 required for interaction with Sin3 have been mapped and subsequently investigated by mutational analysis. In vitro interaction studies could show that amino acids 350-506 of Cti6 bind PAH2 of Sin3. To analyze this Cti6-Sin3 interaction domain (CSID) in more detail, selected amino acids within CSID were replaced by alanine. It turned out that hydrophobic amino acids V467, L481 and L491 L492 L493 are important for Cti6-Sin3 binding. The results of this work also suggest that repression is not executed entirely via Sin3, but rather CSID is also important for contacting pleiotropic corepressor Cyc8. In addition to PAH2 of Sin3, CSID also binds to tetratricopeptide repeats (TPR) of Cyc8. Furthermore, in vitro mapping studies revealed that Fkh1 also binds PAH2 of corepressor Sin3 via its N-terminal domain (aa 51-125). Binding studies with mutagenized Fkh1-Sin3 interaction domain (FSID) showed that Fkh151-125 variants L74A and I78A were unable to bind PAH2 of Sin3. Confirming in vitro studies, Cti6350-506 and Fkh151-125 also displayed in vivo interaction with PAH2 of Sin3 by using the “yeast two -hybrid” system. Chromatin immunoprecipitation (ChIP) analyses have demonstrated Cti6 recruitment to promoters of genes such as RNR3 and SMF3 containing iron responsive elements (IRE). Importantly, Sin3 was also recruited to these promoters but only in the presence of functional Cti6. Similarly, recruitment of Fkh1 and Sin3 to promoters of cell-cycle regulated genes CLB2 and SWI5 was shown. Recruitment of Sin3 was completely Fkh1-dependent. Additional findings of this work shed light on the fact that not only repressor proteins may contact Sin3 but also activator proteins not yet considered for interaction, e. g. specific activators such as Pho4 and Ino2. These findings indicate that Sin3 may fulfill functions beyond acting as a corepressor. In vitro studies on Sin3-Pho4 interaction showed that aa 156-208 of Pho4 are able to bind both PAH1 and PAH2 of Sin3, while an internal region of Ino2 comprising amino acids 119-212 binds to both Sin3 and Cyc8.
In agricultural grasslands, management practice highly determines reproductive success for ground-nesting bird species. The most effective conservation measure is the delay of first mowing dates until broods fledge or bird friendly mowing. Late mowing often implies economical losses for farmers and may increase land use abandonment, which will, in turn, cause habitat deterioration. Thus, grassland bird conservation involves the challenge to protect broods against land use and to promote an appropriate management to sustain habitat quality at the same time. Because of their late and extended breeding season Corncrakes Crex crex are in particular vulnerable to frequent mowing which increases nest destruction, chick mortality and habitat loss.
This thesis aims to gain knowledge on favourable habitat characteristics and brood protection in relation with grassland management to derive implications for the conservation of Corncrake breeding sites in floodplain meadows. Study area is the Lower Oder Valley National Park in northeastern Germany that holds a Corncrake population of 50 to 250 calling males. The study covered two study periods, before (1998-2000) and after (2012-2015) the implementation of new Corncrake conservation measures allowing inferences on the effects of different timing and intensity of mowing for brood protection and habitat conservation.
Breeding was only confirmed on meadows with high forb cover, low sedge cover, low litter heights and a close location to ditches. Radio-tracked females preferred areas with high cover of forbs (> 30%) and a distinct relief heterogeneity, which was associated with increased vegetation diversity. Vegetation characteristics on sites with day calling activity of males showed more similarity with breeding sites than with sites only used for nocturnal calling, supporting the assumption that diurnal calling indicates the occurrence of females. Favoured vegetation structure was best provided by mowing in the preceding year. Low-intensity grazing was less effective in reducing litter and sedge cover, especially when conducted late in the season. In the absence of management, meadows rapidly overgrow and dense litter accumulates from dead plant material in eutrophic floodplains, which increases walking resistance for Corncrakes and may impede prey accessibility. Plant species richness and forb cover declined after land use cessation. Male Corncrakes abandoned calling sites on meadows unmanaged for longer periods.
Besides the availability of suitable nesting sites, food supply and nest predation risk are also related to vegetation structure and may indirectly influence the habitat quality. Faecal samples of Corncrakes consisted mainly of beetles and their larvae, followed by snails, spiders and earthworms. Invertebrate biomass, sampled with pitfall-traps, was twice as high, the numbers of large ground beetles even five times higher on previously unmanaged than on managed meadows. Invertebrate abundance was highest in the first and second years after land use abandonment, but strongly decreased afterwards to a similar level like under annual management. Therefore, unmown refuge strips for Corncrake protection and alternating mowing also enhance invertebrate prey resources in floodplain meadows.
Mammals caused the majority of all observed artificial ground nest predations. Nest predation risk was higher on previously unmanaged than on managed sites. Unmanaged meadows probably attract mammalian predators, because they provide a more favourable vegetation structure for foraging and harbour high numbers of small rodents, increasing also the risk of incidental nest predations. These findings suggest that an annual removal of vegetation, if conducted late in the season to protect grassland birds may reduce predation risk of ground nests in the subsequent year.
Whereas during 1998-2000 half of the study area was managed by the end of July, land use was delayed on meadows occupied by Corncrakes until at least 15 July or 15 August during 2012-2015. On meadows mown between 15 July and 15 August refuge strips were applied. The majority of Corncrake broods were started in the second half of May and mowing postponement until 15 August allows 80% of chicks to fledge without disturbance in the study area. In 65% of broods chicks reach independence (> 14 days old) until 15 July and can be protected by Corncrake friendly mowing because then they are large enough to successfully escape during mowing. Both adults and chicks survived in 10 m wide refuge strips. Because most birds tried to leave the unmown block for the first time when it was up to 30 m wide and only 15 to 30 m wide strips served as temporary habitat for unfledged chicks from mowing to departure, 10 m should be considered as the absolute minimum width for refuge strips.
The strong reduction of land use especially during July should have allowed more chicks to survive until fledging in 2012-2015 than 1998-2000. Besides the protection of nests and higher chick survival, the decline of mowing intensity increased the extent of habitat available for second breeding attempts. In 2012-2015, broods were initiated until late July in the study area. Male Corncrakes showed continuous arrival and departure during the breeding season. Similar departure rates were estimated by a multi-state occupancy model and for radio-tracked males in the same study area and periods, which both left their home ranges spontaneous and due to the impact of mowing. Compared to 1998-2000, total departure of males during June and July was reduced by 50% in 2012-2015, when more calling sites were protected from mowing. Although male Corncrakes show high intra-seasonal dispersal due to their sequential polygamous breeding system, postponed land use should have increased mating opportunities and re-nesting at first breeding sites.
Therefore, future directions of Corncrake conservation in eutrophic floodplains should address the increase of annual late mowing to protect broods and maintain favourable habitat conditions by creating a more flexible mowing regime adjusted to actual occurrence of Corncrakes. This requires expert advice to farmers based on an intense monitoring of calling Corncrakes. Repeated nocturnal surveys during May and June are highly recommended because low detection probability in combination with constant departure substantially underestimated the number of males present. Additionally, diurnal calling activity could improve the identification of breeding sites and timing could be used to estimate chick age in July to select sites for Corncrake friendly mowing. Because currently late mowing dates are unattractive for farmers conservation actions should along with financial compensations for mowing after 15 August promote the utilization of late-cut grass with poor nutrient quality for combustion. Energy production could provide an alternative income for farmers operating in conservation areas with delayed land use dates and will increase their acceptance of Corncrake protection measures.
Peatlands contribute to a wide range of ecosystem services. They play an important role as carbon sinks in their natural state, but when they are drained, they cause carbon emissions. Rewetting drained peatlands is required to reduce carbon emissions and create new carbon sinks. However, drained peatlands are commonly used as grassland or croplands; therefore, alternative agriculture schemes are required following rewetting. Paludiculture, i.e., agriculture on wet and rewetted peatlands, is an option in these areas after rewetting to produce biomass sustainably. Monitoring of peatland management is challenging, yet needed to ensure a successful rewetting and plantation of, e.g., Phragmites australis and Typha spp., two plants which are commonly used in paludiculture. Remote sensing is an excellent tool for monitoring the vegetation composition of vast rewetted peatland regions. However, because many peatland species have similar spectral characteristics, such monitoring is ideally based on high-spatial, high-temporal hyperspectral images. Data that complies with all these requirements does not exist on a regular basis. Therefore, we assessed the potential for mapping peatland vegetation communities in the Peene and Trebel river basins of the federal state of Mecklenburg-Western Pomerania, Germany, using multi-date hyperspectral (PRISMA) data. We used regression-based unmixing to map fractions of different peatland vegetation classes. Results were analyzed with regard to the contribution of multi-date observations and, in comparison, to multispectral datasets (Landsat-8/Sentinel-2). Our results showed that different classes are best mapped at different observation dates. The multi-date hyperspectral datasets produced less Mean Absolute Error (MAE = 16.4%) than the single-date hyperspectral images (ΔMAE + 1%), with high accuracies for all classes of interest. Compared to the results obtained with multispectral data from similar acquisition dates and annual spectral-temporal metrics (STM), the results from hyperspectral data were always clearly superior (ΔMAE + 4%). Besides the superior performance during comparisons, our results also indicate that information that can be derived from the hyperspectral data with the regression-based unmixing goes clearly beyond that of discrete classification. With more hyperspectral sensors coming up and an expected higher availability of multi-data hyperspectral imagery, these data can be expected to play a bigger role in the future monitoring of peatlands.
Species of the genus Wolffia are traditionally used as human food in some of the Asian countries. Therefore, all 11 species of this genus, identified by molecular barcoding, were investigated for ingredients relevant to human nutrition. The total protein content varied between 20 and 30% of the freeze-dry weight, the starch content between 10 and 20%, the fat content between 1 and 5%, and the fiber content was ~25%. The essential amino acid content was higher or close to the requirements of preschool-aged children according to standards of the World Health Organization. The fat content was low, but the fraction of polyunsaturated fatty acids was above 60% of total fat and the content of n-3 polyunsaturated fatty acids was higher than that of n-6 polyunsaturated fatty acids in most species. The content of macro- and microelements (minerals) not only depended on the cultivation conditions but also on the genetic background of the species. This holds true also for the content of tocopherols, several carotenoids and phytosterols in different species and even intraspecific, clonal differences were detected in Wolffia globosa and Wolffia arrhiza. Thus, the selection of suitable clones for further applications is important. Due to the very fast growth and the highest yield in most of the nutrients, Wolffia microscopica has a high potential for practical applications in human nutrition.
Analysis and Reduction of Cellular Heterogeneity in Strain Optimization of Bacillus licheniformis
(2021)
Bacillus species invest substantial resources in inherent cellular processes for pre-adaptation to environmental changes, many of which are dispensable in the controlled environment of industrial bioprocesses. The underlying physiological mechanisms are well characterized in B. subtilis, but only little is known about these processes in the closely related B. licheniformis. Moreover, experimental conditions in previous studies differ from industrial settings in most parameters, foremost in batch cultures or plate-based analysis over fed-batch processes. In this thesis, cellular heterogeneity was analyzed in B. licheniformis in optimized, nutrient-rich media in batch and fed-batch cultivations. Systematic inactivation of genes involved in biofilm formation and synthesis of the flagellar apparatus or global regulators thereof resulted in higher protein production and provided new insights into biofilm formation and cellular heterogeneity in this strain.
Humans consume snail flesh as part of their diet. To assess its nutritional value and toxicity, chemical analyses were conducted to confirm the presence of protein, total and reduced carbohydrates, fat, fatty acid composition and mineral components. Furthermore, an acute toxicity study was carried out to determine the safety of Helix aspersa Müller snail flesh. H. aspersa Müller snail flesh exhibits a high nutritional content, a good ω3/ω6 ratio and higher levels of unsaturated fatty acids. Various minerals have been found in the flesh of H. aspersa Müller. Around 76.91 kcal, or 3.84% of the energy of a daily meal of 2000 kcal, are present in 100 g of this flesh. The evaluation of the antioxidant capacity indicated that the flesh’s extracts contained a large quantity of antioxidant biomolecules. Administration of the aqueous extract of H. aspersa Müller flesh didn’t cause death in laboratory rats, indicating that the lethal dose 50 is greater than 2000 mg·kg−1 body weight. The consumption of the flesh of H. aspersa Müller is highly recommended for human consumption due to its high concentration of nutrients and essential elements, as well as unsaturated fats, and due to its safety.
Amine transaminases (ATAs) are powerful biocatalysts for the stereoselective synthesis of chiral amines. Machine learning provides a promising approach for protein engineering, but activity prediction models for ATAs remain elusive due to the difficulty of obtaining high-quality training data. Thus, we first created variants of the ATA from Ruegeria sp. (3FCR) with improved catalytic activity (up to 2000-fold) as well as reversed stereoselectivity by a structure-dependent rational design and collected a high-quality dataset in this process. Subsequently, we designed a modified one-hot code to describe steric and electronic effects of substrates and residues within ATAs. Finally, we built a gradient boosting regression tree predictor for catalytic activity and stereoselectivity, and applied this for the data-driven design of optimized variants which then showed improved activity (up to 3-fold compared to the best variants previously identified). We also demonstrated that the model can predict the catalytic activity for ATA variants of another origin by retraining with a small set of additional data.
Protein engineering is essential for altering the substrate scope, catalytic activity and selectivity of enzymes for applications in biocatalysis. However, traditional approaches, such as directed evolution and rational design, encounter the challenge in dealing with the experimental screening process of a large protein mutation space. Machine learning methods allow the approximation of protein fitness landscapes and the identification of catalytic patterns using limited experimental data, thus providing a new avenue to guide protein engineering campaigns. In this concept article, we review machine learning models that have been developed to assess enzyme-substrate-catalysis performance relationships aiming to improve enzymes through data-driven protein engineering. Furthermore, we prospect the future development of this field to provide additional strategies and tools for achieving desired activities and selectivities.
Introduction
Given rapid global population aging, developing interventions against age-associated cognitive decline is an important medical and societal goal. We evaluated a cognitive training protocol combined with transcranial direct current stimulation (tDCS) on trained and non-trained functions in non-demented older adults.
Methods
Fifty-six older adults (65–80 years) were randomly assigned to one of two interventional groups, using age and baseline performance as strata. Both groups performed a nine-session cognitive training over 3 weeks with either concurrent anodal tDCS (atDCS, 1 mA, 20 minutes) over the left dorsolateral prefrontal cortex (target intervention) or sham stimulation (control intervention). Primary outcome was performance on the trained letter updating task immediately after training. Secondary outcomes included performance on other executive and memory (near and far transfer) tasks. All tasks were administered at baseline, post-intervention, and at 1- and 7-month follow-up assessments. Prespecified analyses to investigate treatment effects were conducted using mixed-model analyses.
Results
No between-group differences emerged in the trained letter updating and Markov decision-making tasks at post-intervention and at follow-up timepoints. Secondary analyses revealed group differences in one near-transfer task: Superior n-back task performance was observed in the tDCS group at post-intervention and at follow-up. No such effects were observed for the other transfer tasks. Improvements in working memory were associated with individually induced electric field strengths.
Discussion
Cognitive training with atDCS did not lead to superior improvement in trained task performance compared to cognitive training with sham stimulation. Thus, our results do not support the immediate benefit of tDCS-assisted multi-session cognitive training on the trained function. As the intervention enhanced performance in a near-transfer working memory task, we provide exploratory evidence for effects on non-trained working memory functions in non-demented older adults that persist over a period of 1 month.
The combination of repeated behavioral training with transcranial direct current stimulation (tDCS) holds promise to exert beneficial effects on brain function beyond the trained task. However, little is known about the underlying mechanisms. We performed a monocenter, single-blind randomized, placebo-controlled trial comparing cognitive training to concurrent anodal tDCS (target intervention) with cognitive training to concurrent sham tDCS (control intervention), registered at ClinicalTrial.gov (Identifier NCT03838211). The primary outcome (performance in trained task) and secondary behavioral outcomes (performance on transfer tasks) were reported elsewhere. Here, underlying mechanisms were addressed by pre-specified analyses of multimodal magnetic resonance imaging before and after a three-week executive function training with prefrontal anodal tDCS in 48 older adults. Results demonstrate that training combined with active tDCS modulated prefrontal white matter microstructure which predicted individual transfer task performance gain. Training-plus-tDCS also resulted in microstructural grey matter alterations at the stimulation site, and increased prefrontal functional connectivity. We provide insight into the mechanisms underlying neuromodulatory interventions, suggesting tDCS-induced changes in fiber organization and myelin formation, glia-related and synaptic processes in the target region, and synchronization within targeted functional networks. These findings advance the mechanistic understanding of neural tDCS effects, thereby contributing to more targeted neural network modulation in future experimental and translation tDCS applications.
Bacillus subtilis has been extensively used as a microbial cell factory for industrial enzymes due to its excellent capacities for protein secretion and large-scale fermentation. This bacterium is also an attractive host for biopharmaceutical production. However, the secretion potential of this organism is not fully utilized yet, mostly due to a limited understanding of critical rearrangements in the membrane proteome upon high-level protein secretion. Recently, it was shown that bottlenecks in heterologous protein secretion can be resolved by genome minimization. Here, we present for the first time absolute membrane protein concentrations of a genome-reduced B. subtilis strain (“midiBacillus”) expressing the immunodominant Staphylococcus aureus antigen A (IsaA). We quantitatively characterize the membrane proteome adaptation of midiBacillus during production stress on the level of molecules per cell for more than 400 membrane proteins, including determination of protein concentrations for ∼61% of the predicted transporters. We demonstrate that ∼30% of proteins with unknown functions display a significant increase in abundance, confirming the crucial role of membrane proteins in vital biological processes. In addition, our results show an increase of proteins dedicated to translational processes in response to IsaA induction. For the first time reported, we provide accumulation rates of a heterologous protein, demonstrating that midiBacillus secretes 2.41 molecules of IsaA per minute. Despite the successful secretion of this protein, it was found that there is still some IsaA accumulation occurring in the cytosol and membrane fraction, leading to a severe secretion stress response, and a clear adjustment of the cell’s array of transporters. This quantitative dataset offers unprecedented insights into bioproduction stress responses in a synthetic microbial cell.
Microbial cell factories have been largely exploited for the controlled production of recombinant proteins, including industrial enzymes and biopharmaceuticals. The advent of high-throughput ‘-omics’ techniques have boosted the design of these production systems due to their valuable contribution to the field of systems metabolic engineering, a discipline integrating metabolic engineering with systems and synthetic biology. In order to thrive, the field of systems metabolic engineering needs absolute proteomics data to be generated, as proteins are the central players in the complex metabolic and adaptational networks. Due to advent of mass spectrometry-based proteomics, a substantial amount of absolute proteomic data became available in the past decade. However, membrane proteins remained inaccessible to these efforts.
Nonetheless, comparative studies targeting the membrane proteome have been quite successful in characterizing physiological processes. Hence, label-free proteomics was used in a study (Quesada-Ganuza et al, 2019 – Article I) to identify and optimize PrsA in Bacillus subtilis, for improved yield of amylase. Amylase is one of the most relevant enzymes in the biotechnological sector. By employing a label-free mass spectrometry approach targeting the membrane proteome of this bacterium, relative changes in heterologous and native levels of PrsA could be quantified. The results of this study evidenced that each PrsA shows different relative abundancies, but with no relevant impact in the yield of amylase.
Even though relative protein quantification can already provide a good visualization of the physiological changes occurring between different conditions, they are not sufficient to understand how resources are allocated in the cell under certain physiological conditions. Therefore, a global method for absolute membrane protein quantification remains the biggest requirement for systems metabolic engineering.
Hence, with this work, we successfully developed a mass spectrometry-based approach enabling the absolute quantification of membrane proteins (Antelo-Varela et al, 2019 – Article II). This study was also performed in the Gram-positive model organism Bacillus subtilis, regarded as a prolific microbial cell factory. The method developed in this work combines the comprehensiveness of shotgun proteomics with the sensitivity and accuracy of targeted mass spectrometry. Fundamental to the method is that it relies on the application of a correction and an enrichment factor to calibrate absolute membrane protein abundances derived from shotgun mass spectrometry. This has permitted, for the first time reported, the calculation of absolute membrane protein abundances in a living organism.
The newly developed approach enabled to accurately quantify ~40% of the predicted proteome of this bacterium, offering a clear visualization of the physiological rearrangements occurring upon the onset of osmotic stress. In addition, this work also provides evidence for new membrane protein stoichiometries.
Overall, this study enabled the development of a straightforward methodology long-needed in the scientific and biotechnological community and, for the first time reported, providing absolute abundances of one of the most puzzling fractions of the cell – the membrane proteome.
The next step of the work summarized here was to implement the afore described method to a biotechnological relevant strain, as absolute membrane protein abundances are essential to understand the fundamental principles of protein secretion and production stress. Hence, this work was applied in a genome-reduced B. subtilis strain, ‘midiBacillus’, expressing the major staphylococcal antigen IsaA (Antelo-Varela et al, submitted – Article III). The employed absolute membrane protein quantification methodology enabled the analysis of physiological rearrangements occurring upon the induction of heterologous protein production. This work showed that, even though IsaA was successfully secreted into the growth medium, one of the main requirements for the biotechnological sector, it was still partly accumulated in the cell membrane of this bacterium. This led to an exacerbated physiological response where membrane proteins involved in the management of secretion stress were activated. In addition, this study also showed that a rearrangement of the cell’s translocation machinery occurs upon induction of production, where a ‘game’ of in- and decrease of transporters takes place.
Anticipating the impact of genetic and environmental insults, such as the ones caused by production stress, is essential for the field of systems metabolic engineering. Thus, the highly accurate and comprehensive dataset generated during this work can be implemented in predictive mathematical models, thereby contributing in the rational design of next-generation secretion systems.
Significance of Hyperbaric Oxygenation in the Treatment of Fournier’s Gangrene: A Comparative Study
(2018)
Introduction: Hyperbaric oxygenation (HBO), in addition to anti-infective and surgical therapy, seems to be a key treatment point for Fournier’s gangrene. The aim of this study was to investigate the influence of HBO therapy on the outcome and prognosis of Fournier’s gangrene. Patients and Methods: In the present multicenter, retrospective observational study, we evaluated the data of approximately 62 patients diagnosed with Fournier’s gangrene between 2007 and 2017. For comparison, 2 groups were distinguished: patients without HBO therapy (group A, n = 45) and patients with HBO therapy (group B, n = 17). The analysis included sex, age, comorbidities, clinical symptoms, laboratory and microbiological data, debridement frequency, wound dressing, antibiotic use, outcome and prognosis. The statistical analysis was performed with GraphPad Prism 7® (GraphPad Software, Inc., La Jolla, USA). Results: Demographic data showed no significant differences. The laboratory parameters C-reactive protein and urea were significantly higher in group B (group B: 301.7 vs. 140.6 mg/dL; group A: 124.8 vs. 54.7 mg/dL). Sepsis criteria were fulfilled in 77.8 and 100% of the patients in groups A and B respectively. Treatment in the intensive care unit (ICU) was therefore indicated in 69% of the patients in group A and 100% of the patients in group B. The mean ICU stay was 9 and 32 days for patients in groups A and B respectively. The wound debridement frequency and hospitalization stay were significantly greater in group B (13 vs. 5 debridement and 40 vs. 22 days). Initial antibiosis was test validated in 80% of the patients in group A and 76.5% of the patients in group B. Mortality was 0% in group B and 4.4% in the group A. Conclusion: The positive influence of HBO on the treatment of Fournier’s gangrene can be estimated only from the available data. Despite poorer baseline findings with comparable risk factors, mortality was 0% in the HBO group. The analysis of a larger patient cohort is desirable to increase the significance of the results.
Significance of Hyperbaric Oxygenation in the Treatment of Fournier’s Gangrene: A Comparative Study
(2018)
Introduction: Hyperbaric oxygenation (HBO), in addition to anti-infective and surgical therapy, seems to be a key treatment point for Fournier’s gangrene. The aim of this study was to investigate the influence of HBO therapy on the outcome and prognosis of Fournier’s gangrene. Patients and Methods: In the present multicenter, retrospective observational study, we evaluated the data of approximately 62 patients diagnosed with Fournier’s gangrene between 2007 and 2017. For comparison, 2 groups were distinguished: patients without HBO therapy (group A, n = 45) and patients with HBO therapy (group B, n = 17). The analysis included sex, age, comorbidities, clinical symptoms, laboratory and microbiological data, debridement frequency, wound dressing, antibiotic use, outcome and prognosis. The statistical analysis was performed with GraphPad Prism 7® (GraphPad Software, Inc., La Jolla, USA). Results: Demographic data showed no significant differences. The laboratory parameters C-reactive protein and urea were significantly higher in group B (group B: 301.7 vs. 140.6 mg/dL; group A: 124.8 vs. 54.7 mg/dL). Sepsis criteria were fulfilled in 77.8 and 100% of the patients in groups A and B respectively. Treatment in the intensive care unit (ICU) was therefore indicated in 69% of the patients in group A and 100% of the patients in group B. The mean ICU stay was 9 and 32 days for patients in groups A and B respectively. The wound debridement frequency and hospitalization stay were significantly greater in group B (13 vs. 5 debridement and 40 vs. 22 days). Initial antibiosis was test validated in 80% of the patients in group A and 76.5% of the patients in group B. Mortality was 0% in group B and 4.4% in the group A. Conclusion: The positive influence of HBO on the treatment of Fournier’s gangrene can be estimated only from the available data. Despite poorer baseline findings with comparable risk factors, mortality was 0% in the HBO group. The analysis of a larger patient cohort is desirable to increase the significance of the results.
Objective: The study aimed to test the reliability of a semi-structured telephone interview for the classification of headache disorders according to the ICHD-3.
Background: Questionnaire-based screening tools are often optimized for single primary headache diagnoses [e.g., migraine (MIG) and tension headache (TTH)] and therefore insufficiently represent the diagnostic precision of the ICHD-3, which limits epidemiological research of rare headache disorders. Brief semi-structured telephone interviews could be an effective alternative to improve classification.
Methods: A patient population representative of different primary and secondary headache disorders (n = 60) was recruited from the outpatient clinic (HSA) of a tertiary care headache center. These patients completed an established population-based questionnaire for the classification of MIG, TTH, or trigeminal autonomic cephalalgia (TAC). In addition, they received a semi-structured telephone interview call from three blinded headache specialists individually. The agreement of diagnoses made either using the questionnaires or interviews with the HSA diagnoses was evaluated.
Results: Of the 59 patients (n = 1 dropout), 24% had a second-order and 5% had a third-order headache disorder. The main diagnoses were as follows: frequent primary headaches with 61% MIG, 10% TAC, 9% TTH, and 5% rare primary and 16% secondary headaches. Second-order diagnosis was chronic migraine throughout, and third-order diagnoses were medication overuse headache and TTH. Agreement between main headaches from the HSA was significantly better for the telephone interview than for the questionnaire (questionnaire: κ = 0.330; interview: κ = 0.822; p < 0.001). Second-order diagnoses were not adequately captured by questionnaires, while there was a trend for good agreement with the telephone interview (κ = 0.433; p = 0.074). Headache frequency and psychiatric comorbidities were independent predictors of HSA and telephone interview agreement. Male sex, headache frequency, severity, and depressive disorders were independently predictive for agreement between the questionnaire and HSA. The telephone interview showed high sensitivity (≥71%) and specificity (≥92%) for all primary headache disorders, whereas the questionnaire was below 50% in either sensitivity or specificity.
Conclusion: The semi-structured telephone interview appears to be a more reliable tool for accurate diagnosis of headache disorders than self-report questionnaires. This offers the potential to improve epidemiological headache research and care even in underserved areas.
Abstract
Purpose
This study aims to assess the implementation of published research, contraindications, and warnings on the prescription of dual renin‐angiotensin‐hormone system (RAS) blockade in ambulatory care in Germany.
Methods
Cohort study based on health claims data of 6.7 million subjects from 2008 to 2015. Yearly prevalence and incidence for dual RAS blockade with (a) angiotensin‐converting enzyme inhibitors and angiotensin‐receptor blockers (ACEI + ARB) and (b) aliskiren and ACEI or ARB (aliskiren + ACEI/ARB) were calculated. We assessed prescriber specialty and associations between discontinuing dual RAS blockade with specialist (internal medicine, cardiology, nephrology) visits and hospital discharge in the previous year.
Results
A total of 2 984 517 patients were included (age 51.4 ± SD 18.4 y, 48.5% male). Prescription rates for ACEI + ARB decreased from 0.6% (n = 17 907) to 0.4% (n = 12 237) and for aliskiren + ACEI/ARB from 0.23% (n = 6634) to 0.03% (n = 818). Incident prescriptions decreased from 0.23% (n = 6705) to 0.19% (n = 5055) (ACE + ARB) and from 0.1% (n = 2796) to 0.005% (n = 142) (aliskiren + ACE/ARB); 59% of ACEI + ARB and 48% of aliskiren + ACE/ARB combinations were prescribed only by one physician. Of those, 73% (ACEI + ARB) and 58% (aliskiren + ACE/ARB) were primary care providers (PCPs). Discontinuing dual RAS blockade was associated with specialist care and hospital discharge in the previous year (specialist care: RR 1.4, 95% CI, 1.3‐1.6; hospital visit: RR 1.5, 95% CI, 1.3‐1.6).
Conclusions
Our results suggest a delayed uptake of treatment recommendation for ACEI + ARB and a higher impact of Dear Doctor letters addressing PCPs directly compared with published research, contraindications, and warnings. Targeted continuous medical education, practice software alerts, and stronger involvement of pharmacists might improve the implementation of medication safety recommendations in ambulatory care.
Herein, we report the synthesis of a series of push–pull imines by considering cyclic diamino substituent at the C‐centre and fluoroaryl substituent at the N‐centre. This has been achieved by a selective aromatic nucleophilic substitution of different fluoroarenes by N‐H‐substituted N‐heterocyclic imines (NHIs) at ambient conditions without any additional reagent. Solid‐state molecular structure analysis reveals the elongation of the central C–N bond of the imine functionality, which is consistent with the push–pull nature of these imines. The push–pull nature of these imines is further validated by computational studies.
Effectiveness of Varenicline as an Aid to Smoking Cessation in Primary Care: An Observational Study
(2012)
Aims: Although varenicline is commonly prescribed in primary care, information on smoking-related comorbidities and the effectiveness of varenicline in this context in Germany is scarce. This study assessed the efficacy and safety of varenicline in a large sample of patients seeking smoking cessation treatment through their general practitioners. The frequency of comorbidities was also evaluated. Methods: This was a 12-week, prospective, observational, non-comparative phase IV trial conducted in Germany. Abstinence rates at week 12 were evaluated by verbal reporting using the nicotine use inventory. Results: Overall, 1,391 subjects were enrolled; 1,177 received study medication and were evaluated for effectiveness and safety. At the end of the study, 71.1% (95% confidence interval 68.5–73.7) of subjects were abstinent. There were a total of 205 all-causality adverse events; 2.2% were classified as serious or severe. There were no fatal adverse events. At inclusion, 66.7% of participants had at least 1 concurrent comorbidity, with chronic obstructive pulmonary disease (35.5%), hypertension (29.6%) and depression (10.4%) being the most commonly reported. Conclusion: These real-world data indicate that varenicline is an effective and well-tolerated smoking cessation treatment when used in the primary care setting including patients with smoking-related comorbidities.
Growth, ageing and atherosclerotic plaque development alter the biomechanical forces acting on the vessel wall. However, monitoring the detailed local changes in wall shear stress (WSS) at distinct sites of the murine aortic arch over time has been challenging. Here, we studied the temporal and spatial changes in flow, WSS, oscillatory shear index (OSI) and elastic properties of healthy wildtype (WT, n = 5) and atherosclerotic apolipoprotein E-deficient (Apoe−/−, n = 6) mice during ageing and atherosclerosis using high-resolution 4D flow magnetic resonance imaging (MRI). Spatially resolved 2D projection maps of WSS and OSI of the complete aortic arch were generated, allowing the pixel-wise statistical analysis of inter- and intragroup hemodynamic changes over time and local correlations between WSS, pulse wave velocity (PWV), plaque and vessel wall characteristics. The study revealed converse differences of local hemodynamic profiles in healthy WT and atherosclerotic Apoe−/− mice, and we identified the circumferential WSS as potential marker of plaque size and composition in advanced atherosclerosis and the radial strain as a potential marker for vascular elasticity. Two-dimensional (2D) projection maps of WSS and OSI, including statistical analysis provide a powerful tool to monitor local aortic hemodynamics during ageing and atherosclerosis. The correlation of spatially resolved hemodynamics and plaque characteristics could significantly improve our understanding of the impact of hemodynamics on atherosclerosis, which may be key to understand plaque progression towards vulnerability.
Abstract
Aims
Pinus uncinata is the major treeline‐forming species in the Pyrenees. Yet, the role of its reproduction and dispersal as drivers of treeline dynamics remains unknown. Here we quantify seed production, dispersal and germination changes along the elevation gradient to assess whether they may constrain the foreseen treeline advance in the Pyrenees.
Location
Central Pyrenees, Catalonia, NE Spain.
Methods
We established four plots along an elevation gradient from the closed subalpine forest to the krummholz zone at five study sites. In each plot, we collected cones from five to six trees, measured their length, and triggered their opening in the laboratory to count the number of empty seeds and the number and weight of full seeds. We used the collected seeds in a germination experiment under controlled conditions in growth chambers. Additionally, we installed seed traps along the forest–alpine grassland transition to measure seed rain for three consecutive years in three of the study sites.
Results
The number of full seeds per cone decreased along the elevation gradient and was correlated with cone length. However, the proportion of full seeds per cone and their weight did not differ between elevation positions. Seed rain decreased drastically with elevation and no seeds arrived into the alpine grassland traps consistently across study years. Although germination success did not significantly differ between elevation provenances (i.e., elevation position of origin), we found significant differences in germination dynamics between study sites and between elevation provenances within sites.
Conclusions
Our results indicate that whereas the viability of Pinus uncinata seeds is not limited by elevation, seed production and dispersal are constraining the ongoing rates of treeline advance in the Pyrenees.
Human-driven peatland drainage has occurred in Europe for centuries, causing habitat degradation and leading to the emission of greenhouse gases. As such, in the last decades, there has been an increase in policies aiming at restoring these habitats through rewetting. Alder (Alnus glutinosa L.) is a widespread species in temperate forest peatlands with a seemingly high waterlogging tolerance. Yet, little is known about its specific response in growth and wood traits relevant for tree functioning when dealing with changing water table levels. In this study, we investigated the effects of rewetting and extreme flooding on alder growth and wood traits in a peatland forest in northern Germany. We took increment cores from several trees at a drained and a rewetted stand and analyzed changes in ring width, wood density, and xylem anatomical traits related to the hydraulic functioning, growth, and mechanical support for the period 1994–2018. This period included both the rewetting action and an extreme flooding event. We additionally used climate-growth and climate-density correlations to identify the stand-specific responses to climatic conditions. Our results showed that alder growth declined after an extreme flooding in the rewetted stand, whereas the opposite occurred in the drained stand. These changes were accompanied by changes in wood traits related to growth (i.e., number of vessels), but not in wood density and hydraulic-related traits. We found poor climate-growth and climate-density correlations, indicating that water table fluctuations have a stronger effect than climate on alder growth. Our results show detrimental effects on the growth of sudden water table changes leading to permanent waterlogging, but little implications for its wood density and hydraulic architecture. Rewetting actions should thus account for the loss of carbon allocation into wood and ensure suitable conditions for alder growth in temperate peatland forests.
Infections with Helicobacter pylori are a global challenge that affects both developed and developing countries. This infection is currently treated using multiple antimicrobials that are mostly absorbed after oral administration and subsequently secreted into the gastric lumen. The eradication rates from the different therapeutic regimens, however, are declining nowadays, primarily due to high antibiotic resistance and possibly the mode of drug delivery. H. pylori is commonly found adhering to epithelial cells, and therefore, intragastric drug delivery may be a more direct treatment option. In this work, we developed a new strategy for the local eradication of H. pylori within the stomach.
Initial in vitro experiments revealed that penicillin G shows promising antibiotic activity against resistant strains of H. pylori with MIC values of 0.125 µg/mL. To provide luminal concentrations above the MIC for an extended time, we decided to follow two different formulation strategies: effervescent granules and HPMC-based hydrogel matrix tablets. Among the granule formulations, only one batch was stable and demonstrated excellent performance with respect to drug content, effervescent action, and drug release. It was therefore selected for further in vitro studies. All matrix tablets showed the desired tablet quality requirements and drug release was scalable in vitro by the HPMC concentration.
In order to quantify PGS in various formulations and media, an HPLC method was developed and validated. Due to the stability concerns, the degradation behavior of PGS was studied at different pH. PGS was found to be unstable at acidic pH values, but its stability was higher at more neutral pH values. Sufficient stability was exhibited at pH values above pH 4.5. Due to the instability of PGS in acidic media, alkalizers were added to the matrix tablets to prevent the degradation of the drug within the tablet. Among the alkalizers tested, NaHCO3 showed the most promising results as it significantly enhanced the stability within the matrix and also the concentration of PGS in the dissolution media. The stabilizing effect was caused mainly by the modulation of the microenvironmental pH rather than a pH change in the dissolution media. As a result, these matrix tablets were selected for further in vitro characterization.
In order to guide formulation development, a flow-through model (FTM), which was able to simulate various physiological conditions of the gastric environment, was developed and applied. In contrast to compendial dissolution methods, the FTM allowed studying the effect of gastric secretion, mixing and emptying on the gastric concentration of the drug in vitro. It could be shown that the granules generated a high initial concentration, which decreased over time. On the contrary, the matrix tablets did not provide such a profile due to the absence of pressure events in the model. Further investigations of the matrix tablets in a dissolution stress test device revealed faster drug release if pressure events of physiological relevance are simulated.
In the last part of this thesis, the two formulation concepts were compared in vivo by using the salivary tracer technique. For this purpose, caffeine was used as a model drug. The in vivo investigations suggested that granules administered in a fed state demonstrated longer gastric retention than in a fasted state. In a fed state, effervescent granules provided longer gastric retention of caffeine in comparison to the matrix tablets. Interestingly, the administration of the granules together with 240 mL of tap water provided an even better gastric retention of caffeine than the smaller volume (20 mL). Additional MRI investigations after 4 h of tablets’ intake revealed that the matrix tablets were already disintegrated in vivo.
In conclusion, effervescent granules dosed after food are expected to better maintain intragastric drug concentration over an extended period compared to matrix tablets. Moreover, the carbon dioxide generated after disintegration supports the mixing of the drug with the chyme and thus, provides a uniform distribution of the drug. By this, bacterial sanctuary sites within the stomach can be avoided. The major challenge could be the stability of PGS in acidic media. This problem could be addressed via concomitant administration of PPIs. H2 blockers could also be recommended to address nocturnal acid-breakthrough during the mid-night. In combination with an acid-reducing agent, PGS granule formulations alone or part of the treatment regimens could enable the local eradication of H. pylori directly within the stomach.
Objectives:
This study investigates the effectiveness of the Cold AP on the alteration of the enamel surface
without using acid etchant by using Conventional photo-activated resin bond to bond the
orthodontic brackets.
Materials and Methods:
One hundred and twenty-five Enamel specimens are prepared from disinfected bovine
mandibular incisors are divided into five groups. Group I: brackets are attached on the enamel
surface with the standard adhesive technique (etch + primer +bond). Group II: the brackets are
attached with the Standard Orthodontic adhesive technique without etching. Group III: the
enamel surface is conditioned with pure Argon Cold atmospheric plasma before the application
of the primer without using an acid etchant. Group IV: the enamel surface is conditioned with
the admixture of Argon Cold atmospheric plasma with 0.5 % Oxygen before the application of
the primer without using acid etchant Group V: after the application of Argon Cold atmospheric
plasma with 0.5 % Oxygen the surface is rewetted by deionized water before the application
of the primer and adhesive. After that, the samples are exposed to thermal cycling. The shear
bond strength of the samples is tested by the universal testing machine which measured the
maximum force at which the brackets are deboned from the tooth surface at a speed of
1mm/minute is measured.
Results:
Significant intergroup differences were found. Group V showed the highest shear bond
strength followed by Group I, VI, III, II respectively. There isn’t a statistical difference in the
values of The Shear bond strength values between Group III and IV.
Conclusions:
this study implies that Cold Atmospheric Plasma is a safe method to change the chemical
surface characteristics of the enamel surface.in addition to the significant importance of plasma
treatment followed by water rewetting, which could enhance adhesion between the orthodontic
attachments and the enamel layer
In this study we investigated the synergistic antimicrobial effect of a dual protocol combining cold atmospheric pressure plasma (CAP) and antimicrobial photodynamic therapy (aPDT) against different planktonic bacterial and yeast species including methicillin-sensitive and methicillin-resistant Staphylococcus aureus, Escherichia coli, extended-spectrum β-lactamase-positive Escherichia coli and Candida albicans. A DBD plasma device was used for CAP treatment while for aPDT, toluidine blue O (TBO) was the photosensitizer (PS) of choice and a radiator emitting visible and water-filtered-Infrared A light (VIS-wIRA) was used as irradiation source.
Microbial suspensions were either exposed to CAP treatment alone, aPDT treatment alone or aPDT followed by CAP exposure in a dual treatment protocol. Aliquots from each suspension were plated on agar plates and the number of colonies surviving after each treatment was counted. Under the experimental conditions conducted in this study, combining sub-lethal exposure doses of CAP and aPDT treatment showed significantly higher antimicrobial efficacy (P<0.0001) compared to single treatments against all tested microorganisms suggesting a synergistic effect which yielded at least 3.3 log microbial reduction corresponding to 99.6 % microbial death. In the dual CAP-aPDT approach, aPDT did not interfere with CAP-induced acidification of solution, a crucial feature for CAP antimicrobial efficiency, which further confirms the promising clinical potential of this combination regime.
We believe that the CAP-aPDT dual approach described in this study holds great potential as a successful novel antimicrobial and healing-supporting strategy especially when directed for the management of acute and chronic wounds and possibly other skin and soft tissue infections. The use of a VIS-wIRA light source in treating skin infections is preferential, due to the additional therapeutic effects of wIRA in wound healing. Furthermore, the enhanced antimicrobial effects of aPDT when combined with CAP as shown in this study may grant for a reduction in treatment times and costs as well as improving patient compliance.
The aim of this retrospective observational study is to describe and discuss various complications that can arise after insertion of alloplastic materials in the field of urogynecology that require further surgical interventions in order to manage them or to at least improve the quality of life in those women. We were able to collect data on 77 patients who fulfilled the criteria. Medical history, data of clinical findings, and outcomes were collected and analyzed. The most common complication seen as an indication for resecting slings or meshes was de novo overactive bladder syndrome (40%). Other indications seen were lower urinary tract obstruction or obstructive voiding symptoms (21%), chronic pain (21%), and de novo dyspareunia (13%). 36% of the patients had recurrent symptoms (failure) after insertion of alloplastic materials in the form of urinary incontinence or prolapse, 32% presented with vaginal erosions, 2 women had severe signs of infection with abscess formation, another 3 women had urogenital fistulae. Other rare complications after mesh or sling insertion are perforations of the urinary bladder or urethra. Proper case selection is the key factor. The use of meshes and slings seems justified only in patients with known connective tissue weakness and recurrences after native tissue repair. Otherwise, patients will be exposed to unnecessary risk without any expectable improvement to their quality of life. Most of the complications are mainly caused by wrong and inadequate surgical techniques, wrong indications, or missed diagnosis of the underlying problem. In addition, lack of long-term follow-up is usually the cause behind the negligence towards many complications. Therefore, only experienced physicians should be allowed to perform such procedures, and long-term postoperative follow-up is strongly recommended. As slings and meshes are used for procedures of choice as means to improve quality of life, and not for life threatening situations, there is a need for intensive informed consent. All possible alternatives have to be discussed, as do the pros and cons of selected procedures, even the rare complications. Mesh or sling resection is considered to be an effective solution for the management of such complications. It has shown a high success rate in comparison to conservative treatment, and the majority of patients were satisfied and experienced a big improvement in their quality of life. The most common complication after resection is the recurrence of primary symptoms, either urinary incontinence or prolapse. Major or serious intra- or postoperative complications are very rare. All complications were classified and given a code according to the classification system of the international urogynecological association and the international continence society (IUGA/ICS) on 2011. The applicability and practicability of this code were evaluated, looking for ways to possibly improve it or to identify missing parameters. Many patients had more than one code, a problem that entirely torpedoed the idea of “simple” classification. Some complications are not covered individually in the classification, such as failure and recurrence or overactive bladder syndrome. These complications should be included. Many cases began with the same code, despite having different complications. Further sub-classifications should be considered to enable the reader to easily recognize the complication at hand. Patients who came with complications more than one year after mesh or sling insertion were categorized as (T4), regardless of whether the complication arose after 1 year of after 10. Therefore, sub-classifications in the (T4) category are recommended. The “site” category was not applicable in many cases. Furthermore, it is necessary that the severity of a complication is discernible, and should be mentioned in the code. We did not find any correlation between the code given and patient satisfaction. After re-modification and completion, the IUGA/ICS code could be more practical for clinical use, which would allow for the comparison of complications and make the assessment of adverse effects easier for research purposes.
This study explored the evidence of validity of internal structure of the 12-item Functional Assessment of Chronic Illness Therapy—Spiritual Wellbeing Scale (FACIT-Sp-12) in Brazilian adolescents with chronic health conditions. The study involved 301 Brazilian adolescents with cancer, type 1 diabetes mellitus, or cystic fibrosis. Exploratory Factor Analysis (EFA), Confirmatory Factor Analysis (CFA), and Item Response Theory (IRT) were used to test the internal structure. Reliability was determined with Cronbach’s Alpha and McDonald’s Omega. The EFA suggested a one-dimensional scale structure in contrast to the original 2-factor model or the 3-factor model which were not reproduced in the current CFA. All quality indicators for the EFA one-factor exceeded the required criteria (FDI = 0.97, EAP = 0.97, SR = 3.96 and EPTD = 0.96, latent GH = 0.90. and the observed GH = 0.85). The FACIT-Sp-12 for adolescents yielded strong evidence for a 1-factor model and with good reliability.
Background
Self-reported time-use in relation to health-related quality of life (HRQoL) has been widely studied, yet less is known about the directionality of the association and how it compares across genders when controlling for sociodemographic confounders.
Methods
This study focused on the working population of the most recent waves (2013–2018) of the Core-Study of the German Socio-Economic Panel (N = 30,518, 46.70% female, M = 39.24 years). It examined the relationship between three time-use categories (contracted, committed, & leisure time) and HRQoL (self-rated health & life satisfaction) in men and women via multigroup fixed effects cross-lagged panel models. The models controlled for sociodemographic background (age, household income, number of children living in household, employment status, education, & marital status), which was associated with time-use and psychosocial health in previous research.
Results
Contracted time showed consistent positive relationships with HRQoL across genders while associations with the other types of time use differed significantly between men and women and across indicators of HRQoL.
Conclusions
The way we spend our time directly predicts our health perceptions, but in the same vein our health also predicts how we can spend our time. Contracted time in particular was associated with positive HRQoL, across genders, and beyond sociodemographic predictors, highlighting the important role of employment in health, for men and women alike. The impact of commitments beyond contracted time-use—like household chores and childcare—however, continues to affect mainly women, which ultimately reflects in poorer health outcomes.
To a large extent health-related quality of life (HRQoL) is a product of life-course experiences. Therefore, we examined employment, marital, and reproductive life-course typologies as predictors of HRQoL in women and men. To determine life course clusters, sequence and cluster analysis were performed on the annual (waves 1990–2019) employment, marital, and children in household states of the German Socio-Economic Panel data (N = 8,998; age = 53.57, 52.52% female); separately for men and women. Using hierarchical linear regression analyses, and Tukey HSD post-hoc tests, associations between clusters and change in life satisfaction, subjective mental, and physical health were examined. Five life-course clusters were identified in the female and six in the male sample. Life courses differed greatly across gender regarding employment aspects (e.g., men generally work full-time vs. women underwent frequent transitions). The family aspects appeared similar – e.g., ‘starting a family’ or ‘marital separation’ clusters – but still differed in the particulars. Life course typologies were related to distinct patterns of HRQoL. For instance, both for men and women the ‘separated’ clusters, as well as the male ‘entering non-employment’ cluster were associated with a steeper decline in HRQoL. However, change in subjective mental health showed few associations. Distinct types of life courses and differential associations with sociodemographic background and HRQoL emerged for women and men. The analyses reveal a burden on individuals who experienced marital separation, and non-employment and thus present important target groups for health prevention, e.g., for physical health problems.
Until now proximal caries is still a significant problem in the clinical dentistry in spite of the caries decline recently. As resin infiltration offers a new micro-invasive treatment to arrest the progression of proximal initial carious lesions, this study aimed to evaluate its clinical applicability, safety and effect. In the study population of 50 children, adolescents and young adults (mean age 17.9 years ± 6.8), ten dentists at University of Greifswald applied the infiltration material ICON® (DMG, Germany) on non-cavitated proximal lesions in permanent and primary teeth as described in the manual instructions from the producer. The results showed good patient satisfaction with the procedure. The time for the infiltration (24.3 min ± 7.4), which included rubber dam application (7.7 min ± 4), and the effort were perceived as comparable to a composite filling by the dentist or as even easier. In three patients (6%), it was not possible to gain sufficient proximal space for the application of an infiltration. The location of the infiltrated tooth, separation problems as well as the routine of the dentists with the infiltration technique had an effect on the duration of the infiltration. A clear learning curve with a reduction of treatment time for subsequent treatments was observed (P < 0.001). Within the follow-up interval of 12 months, vitality of all infiltrated teeth was still positive and no relevant differences in plaque accumulation or gingival status were recorded. In addition, the infiltrated surfaces showed smooth margins and considerable decrease in the discoloration. In the radiographic evaluation after one year, only two lesions (4.7%) have progressed. Thus, caries infiltration is an applicable method for the treatment of initial non-cavitated proximal lesions without prior temporary tooth separation. Even without special training it can be applied easily by dentist and they experience a clear learning curve within the first 5-10 applications. In addition, the infiltration technique shows a high acceptance by the patients. Furthermore, caries infiltration lead to very good results regarding safety and preventing the lesion progression of non-cavitated proximal caries lesions located in the enamel or in the outer third of dentin.
Eight hundred and fifty two students with an age range 9-13 years (mean 10.34, SD±0.56, 48% females) were recruited from the fifth grade students of different 19 primary schools in Greifswald and East Pomerania. In conjunction with the compulsory dental community examination, additional data were collected with two questionnaires for the children and their parents. Newly generated items were taken from the children’s questionnaire to form short scales for oral health-related knowledge, behaviour, attitudes. Parents’ questionnaire contains questions on socio-economic status (SES) and child’s health. The response rate was 93.2%; 78.8% for children; parents, respectively. Results: The distribution of DMFT values was highly polarized with most of the children (71%) exhibiting no carious defects, fillings or missing teeth in the permanent dentition with a mean of 0.6 ±1.2. There was a significant correlation between DMFT and social class levels (rs=-0.19, p=0.001) with mean DMFT values of 0.9 ± 1.3, 0.6 ±1.1 and 0.4 ± 0.9 for the low, medium and higher social strata, respectively. There was a clear correlation between the dental attitude and dental behaviour (rs=0.32, p=0.003). However, correlations between knowledge vs. attitude and knowledge vs. behaviour were loose. A statistically significant correlation between DMFT and dental behaviour was found (rs=-0.15, p=0.003). It should be noted that children with higher self-esteem were found to have significantly higher dental awareness scores (rs=0.19, p=0.001). General health was a significant predictor for caries incidence (rs=0.08, p=0.01). The frequency of drinking lemonade or ice tea and eating salty snacks (chips, nuts) showed clear correlations with the DMFT (rs=0.17 and 0.13, p<0.01). Prolonged daily TV watching was associated directly with DMFT values (rs=0.13, p=0.001). A significant correlation was found between caries and smoking, even after adjusting for age (rs=0.1, p=0.002). Smoking children had a significantly higher DMFT rate than children who were not smokers with a mean DMFT of 0.9 ±1.5 vs 0.6 ±1.2 (p=0.004). Interestingly, each of prolonged TV watching, more lemonade drinking and smoking were correlated directly with the low socioeconomic status (Spearman correlation coefficient of 0.13, 0.2 and 0.17, respectively, p<0.05). Regarding malocclusion, 64% the subjects had at least one type of anomaly. Crowding and maxillary overjet represented the major proportion 28% and 23%, respectively. Males exhibited significantly higher increased overbite scores than females p=0.04. Whereas the prevalence of crowding was more common in females than males (p=0.05). Amazingly, more malocclusion was registered in children with caries-free primary teeth when compared to children with carious primary teeth (p=0.05). No significant differences in the mean of dmft or DMFT value were found between normal and non normal occlusion (p>0.05). Undergoing to orthodontic treatment was associated with significantly higher dental awareness scores (p=0.003). No correlation between socio-economic status and malocclusion was registered. Conclusion: This thesis confirms the decline and polarisation of dental caries. Dental behaviour was mostly independent of dental knowledge, but depended on dental attitude. Higher scores in dental behaviour resulted in lower DMFT scores; possibly, oral health promotion should strengthen attitude and actual behaviour instead of knowledge. Higher scores in self-esteem and general health connected with lower caries incidence and higher score in dental awareness. Social inequalities was strongly linked with health inequalities with more prevalence of caries, smoking, prolonged TV watching, wrong diet habits and less sealants application among children of low SES. Hence, oral health-related interventions in children sample should be directed at the social structures with more incorporating of oral health promotion programs into other general health promotion programs. This thesis suggests that; the establishment of healthy behaviours such as a regular teeth brushing at school could be one of the most successful ways to involve all children especially children of low SES in dental care. Malocclusion traits were very common in this sample. This underlines the need for more orthodontic preventive programs among children, in order to reducing the risk factors of malocclusion. The association between prevalence of malocclusion and socio economic status could not be established. No generalised conclusion could be drawn about the relationship between caries and malocclusion.
The aim of the present dissertation was to investigate the biological and chemical potential of two European mushroom species: Fomitopsis betulina and Calvatia gigantea. For this purpose, different extracts of both fungi were tested for: antimicrobial, antifungal, cytotoxic, in vitro wound healing, and anti-adhesive properties. Bioassay-guided fractionation led to the isolation of bioactive compounds, altogether 20 compounds were isolated and identified. The compounds were obtained from the ethyl acetate extracts, they included triterpenes, sterols and aromatic compounds. The separated substances from both fungi were proved for biological activities, some of them showed antimicrobial and cytotoxic activities.
Background:
Microvascular decompression (MVD) success rates exceed 90% in hemifacial spasm (HFS).
However, postoperative recovery patterns and durations are variable.
Objective:
We aim to study factors that might influence the postoperative patterns and duration needed until
final recovery.
Method:
Only patients following de-novo MVD with a minimum follow-up of 6 months were included.
Overall trend of recovery was modeled. Patients were grouped according to recognizable clinical
recovery patterns. Uni- and multivariable analyses were used to identify the factors affecting
allocation to the identified patterns and time needed to final recovery.
Results:
323(92.6%) patients had >90% symptom improvement and 269(77.1%) patients had complete
resolution at the last follow–up. The overall trend of recovery showed steep remission within the
first 6 months, followed by relapse peaking around 8 months with a second remission ~16
months. Five main recovery patterns were identified.
Patterns analysis showed that evident proximal indentation of the facial nerve at REZ, males and
facial palsy are associated with earlier recovery at multivariable and univariable levels. AICA,
AICA/VA compressions and shorter disease durations are related to immediate resolution of the
symptoms only on the univariable level. Time analysis showed that proximal indentation (vs.
distal indentation), males and facial palsy witnessed significantly earlier recoveries.
Conclusion:
Our main finding is that in contrast to peripheral indentation, proximal indentation of the facial
nerve at REZ is associated with earlier recovery. Postoperative facial palsy and AICA
compressions are associated with earlier recoveries. We recommend a minimum of 1 year before
evaluating the final outcome of MVD for HFS.
In fixed orthodontic treatments debonding of brackets during treatment is an unpleasant occurrence for the clinician and the patients and resultes in an increase in treatment costs and duration. For Damon Q brackets recycling would considered as an economic saving option which could be done with using of in office methods such as the sandblasting.
A sample of sixty sound bovine first upper central incisers, were collected, cleaned, and mounted in acrylic blocks for shear bond strength testing.
The total sample was equally divided into two main groups. Each group had 30 teeth and 30 brackets.
The first group had 30 teeth bonded with metal Damon Q brackets, the second group had 30 teeth bonded with metal Mini-Mono® brackets.The study included bonding and rebonding experiments. Therefore the same brackets with their same teeth were used in bonding and in the rebonding experiments. The bonding and the rebonding procedures were done with using 3M Unitek etching, Grengloo adhasive, and Ortho solo bonding. In addition the rebonding procedure was done after cleaning the teeth and recycling their brackets with sandblasting. All specimens were recycled 5000 times for the bonding and rebonding experiments.
The first and second debonding forces were done in Newton using a Zwick Roell machine.
After that SBS and SRS were computed in MPa. Furthermore all the teeth, after each debonding, were examined under a digital scanning microscope VHX-5000, 50X magnifying, to performe the ARA and ARI.
The collected data was statistically analyzed for descriptive statistics as well as significance of differences among the different bracket types, and their ARI scores, in the bonding and rebonding experiments.
The results showed that SRS was significantly higher than SBS of both types of the brackets, and Damon Q brackets had higher SBS, and SRS than Mini-Mono® brackets, and there was no correlation between SBS, SRS and their ARI, ARA.
Colonic atresia (CA) is a rare disease with an incidence range between one of 20 000 and one of 66 000 live births. Most CA are located within the proximal colon; distal CA are even rarer. Because of its rarity, another case shall be described herewith. A 37th week of pregnancy born child was noticed occurring multiple vomiting, a distended abdomen and additional whitish-bloody stool shortly thereafter. In the first operation, a double-barrel stoma was created. After sufficient weight gain and alignment of the stoma ends, a secondary anastomosis was created in the child after 2 months. The diagnosis can be made reliably on the basis of an X-ray and leads to a good outcome with prompt surgical intervention. However, accompanying malformations should always be considered.
Objectives: Performing proper toothbrushing is a complicated process for children. Therefore, the aim of this study was to investigate the effect of a smartphone app for improving manual toothbrushing via a gravitation sensor. Methods: In this prospective, controlled, single-blinded, randomized clinical trial, 49 children (mean age 5.1 ± 0.6 years, 27 female) were randomly assigned to test (n = 26) and control (n = 23) groups. All children were provided with manual toothbrushes with an integrated gravitation sensor and they received oral health instructions. Only the children of the test group got an additional smartphone app to visualize and reward proper brushing in form and time. At baseline and recalls after 6 and 12 weeks, plaque and gingival indices (QHI, PBI) were recorded for analysis between the two groups. Results: At baseline, there were no significant differences between the test and control group regarding plaque and gingival indices (QHI: 2.36 ± 0.7 and 2.42 ± 0.8; p = 0.94; PBI: 0.42 ± 0.2 and 0.47 ± 0.3; p = 0.59). At the 6- and 12-week recalls, the test group showed statistically significantly better oral health indices than the controls (6-week recall, QHI: 0.8 ±0.5 and 1.88 ± 0.9; p < 0.001; PBI: 0.08 ± 0.1 and 0.26 ± 0.2; p < 0.001; 12-week recall, QHI: 0.44 ± 0.5 and 1.49 ± 0.7; p < 0.001; PBI: 0.05 ± 0.18 and 0.21 ± 0.1; p < 0.001). Conclusion: The results highlight the enormous possibilities of a toothbrushing application via the smartphone, at least for medium-term oral hygiene improvement in preschool children and even after excluding the app. The long-term effect should also be investigated to exclude the expected novelty effect.
Therapeutic Sealing of Proximal Tooth Surfaces: Two-Year Clinical and Radiographic Evaluation
(2009)
The diagnosis, prevention and treatment of proximal carious lesions comprise a constant problem in clinical dentistry. The purpose of this investigation was to test the safety and clinical effect of a new treatment for proximal caries. In 50 patients with two proximal initial lesions (D1-3 without cavitation, bitewing X-ray), orthodontic rubber rings were applied to gain access to the interproximal space. One of the lesions was sealed with a thin polyurethane-dimethacrylate foil using a bonding agent (Heliobond®, Vivadent, Schaan/Liechtenstein); the other lesion received oral home-care with dental floss and fluoridated toothpaste and was left as control. In clinical follow-ups after 6 and 12 months and X-ray evaluation after two years, clinical retention of proximal tape and the underlying sealant, marginal adaptation, discoloration, tooth vitality, proximal plaque and gingivitis were checked. In addition, caries was assessed clinically and radiographically. The sealants showed good retention, marginal adaptation and colour. After two years, vitality of all teeth was still positive and no relevant differences in plaque accumulation or gingival status were found between sealed and control teeth. Two sealed surface had to be filled due to caries progression (D3 with cavitation). 9 sealed lesions showed caries regression. In contrast, only 4 control lesions regressed and also two showed progression. The loss of tape had no significant influence on the lesion progression indicating the effect of the underlying bond. All other sealants and control lesions were stable indicating an arrest of the lesion. In conclusion, sealing initial proximal lesions showed no clinical problems and mostly arrest of initial carious lesions on bitewing X-rays.
Interoceptive sensations, that means, perceptions of the physiological body state, play an important role in the generation and expression of emotion. The focus of the research presented here is on respiratory sensations as specific interoceptive signals. Such respiratory sensations (like the feeling of dyspnea) play an important role in symptom perception in somatic (e.g., asthma) as well as in mental disorders (e.g., anxiety disorders). There are several different ways to manipulate respiratory sensations in an experimental environment, but many of them did not equal sensations in daily life. Here, stimuli (inspiratory resistive loads, caffeine) were used that trigger nearly naturally occurring interoceptive sensations. Taking into account that the elicited interoceptive experience also induces an unpleasant feeling state it is most likely that individuals show defensive physiological responding to such cues and try to avoid them. According to a bidirectional motivational system defensive behaviors are regulated by a defensive motivational system that is activated by threatening cues. From research with exteroceptive stimuli it is known that defensive responding is typically characterized by heightened autonomic arousal, increased respiration, and a potentiated startle eyeblink response. In contrast, only a few studies using interoceptive stimuli have incorporated the measurement of physiological data in their experimental designs. If included, studies show also heightened autonomic responding, whilst a heterogeneous respiratory as well as startle eyeblink responding is observed. Thus, the studies presented here were designed to clarify the factors that mediate defensive responding to interoceptive sensations. Study 1 investigated the influence of anxiety on the subjective, respiratory, and autonomic response to an individually determined inspiratory resistive load, while study 2 focuses on the effect of attentional modulation of the startle eyeblink response to a mild respiratory threat. In study 3 the modulation of subjective, respiratory and autonomic reactions by arousal expectations was examined. Therefore, caffeine, a respiratory stimulant, or a placebo were administered without the participants’ knowledge. The fourth study examined the influence of the process of worrying, a strategy to deal with unpleasant body symptoms, on defensive responding. Depending on the study design subjective, respiratory and autonomic (skin conductance level, heart rate) parameters were assessed as marker for defensive mobilization. In study 2 and 4 the startle eyeblink response was measured as further index of defensive activation. Besides that in study 2 also the P3 component of the event-related potential, as an index for attentional allocation, was recorded. The main findings of the presented dissertation are the following: Study 1 revealed that 1) only high anxiety sensitive individuals reporting also high suffocation fear respond to lower stimulus intensities with stronger defensive responding, and 2) that this group demonstrated a maladaptive compensatory breathing pattern. Additionally, study 2 exhibited that 1) the startle eyeblink response is relatively inhibited during a mild interoceptive threat, and 2) this inhibition corresponds to an attention allocation towards breathing as indicated by a reduced P3 amplitude to the startle noise as well as subjective report. Furthermore, highly anxiety sensitive individuals showed a more pronounced defensive responding if the interoceptive sensations were unexpected (study 3). Recently, study 4 demonstrated that worry led to an increased defensive response mobilization. All studies are discussed in the context of the theoretical background of the defensive response modulation to exteroceptive and interoceptive sensations with respect to mediating factors. Showing exaggerated defensive responding and maladaptive adaptation processes in high anxious individuals the results point towards the important role of interoceptive sensations in the etiology, maintenance and therapy of mental disorders, especially the anxiety disorders.
Streptococcus pneumoniae (the pneumococcus) is an opportunistic human pathogen that causes life-threatening diseases including pneumonia, sepsis, meningitis but also non-invasive local infections such as otitis media. Pneumococci have evolved versatile strategies to colonize the upper respiratory tract (URT) of humans. Binding to epithelial surfaces is thereby mediated through direct interactions with host cell receptors or indirectly via binding to components of the extracellular matrix (ECM). However, successful colonization and subsequent infection require S. pneumoniae to cross tissue barriers protected by the immune system of the host. Pneumococci have therefore evolved a wide range of mechanisms to circumvent the antibacterial activity of the immune system such as the acquisition or expression of serine protease activity. Serine protease enzymes have emerged during evolution as one of the most abundant and functionally diverse groups of proteins in eukaryotic and prokaryotic organisms. However, the epithelial barriers, integrins, and other cell surface receptors are often initially inaccessible for pneumococci colonizing the nasopharyngeal cavity. Therefore, pneumococci recruit host-derived extracellular serine proteases such as plasmin(ogen) for extracellular matrix and mucus degradation, which results in enhanced binding to epithelial and endothelial cells. S. pneumoniae expresses four surface-anchored or surface-associated serine proteases depending on the serotype: HtrA, SFP, PrtA, and CbpG. These enzymes belong to the category of trypsin-like or subtilisin-like family proteins, which are characterized by the presence of three-conserved amino acid residues, Ser-His-Asp. The catalytic triads are critical for the cleavage of peptide bonds. Studies focusing on the deletion of single pneumococcal serine proteases are difficult to interpret due to the compensatory effects of the other serine proteases.
Initially, a comprehensive in silico analysis of the distribution and genes organization of pneumococcal serine proteases was carried out in this study. Interestingly, the genes encoding PrtA, HtrA, and CbpG were highly conserved among the 11 analyzed strains. Surprisingly, the gene encoding the subtilisin-like protein SFP was not present in some of the strains and seems to be strain-dependent. Therefore, pneumococci have at least three serine proteases as shown e.g., for serotype 19F_EF3030 strain. Computer-assisted analyses of the structure of pneumococcal serine proteases showed high similarities in the catalytic domains between HtrA and CbpG or between PrtA and SFP in 3D structural models.
The focus of this study lies on the impact of single extracellular pneumococcal serine proteases on pneumococcal pathogenesis during adherence, colonization, virulence and biofilm formation. Therefore, double and triple deletion mutants were generated in the colonizing S. pneumoniae serotype 19F strain EF3030 and the more invasive serotype 4 strain TIGR4, respectively. In adherence studies with human Detroit-562 epithelial cells, we demonstrated that both TIGR4Δcps and 19F_EF3030 mutants without serine proteases or expressing only CbpG, HtrA, or PrtA have a reduced ability to adhere to Detroit-562 cells. In a mouse colonization model, the inactivation of serine proteases in strain 19F_EF3030 strongly reduced nasopharyngeal colonization in CD-1 mice. The bacterial load in the nasopharynx was thereby monitored for a period of 14 days. Mutant strains showed significantly lower bacterial numbers in the nasopharynx on days 2, 3, 7, and 14 post-inoculations.
Following up on pneumococcal pathogenesis, an in vivo acute pneumonia mouse infection model and in vitro phagocytosis was used to analyze the impact of single serine proteases during infection and phagocytosis. Mice were intranasally infected with the bioluminescent TIGR4lux wild-type or isogenic triple mutants expressing only CbpG, HtrA, PrtA, or SFP. The acute lung infection was monitored in real-time by using an IVIS®-Spectrum in vivo imaging system. The TIGR4lux mutant expressing only PrtA showed a significant attenuation and was less virulent in the acute pneumonia model. Phagocytosis assays were conducted using murine J77A.1 macrophages. The number of triple serine protease mutants internalized by macrophages were significantly reduced in comparison to the isogenic wild-type.
Finally, two different experimental biofilm models were used to study the influence of serine proteases on biofilm formation grown on an abiotic surface (glass) and a biological surface. Biofilm development on living epithelial cells was stronger after 48 and 72h than on the glass surface. On epithelial substratum, the serine protease mutant with only CbpG+ showed higher and denser biofilm development after 48h and 72h of incubation compared to the parental strains and other serine protease mutants. Moreover, the bacterial dispersal from biofilms was significantly more in the mutant strains lacking serine proteases than in the wild type.
In conclusion, nasopharyngeal colonization is a prerequisite for invasive diseases and transmission. Pneumococcal serine proteases are indispensable for nasopharyngeal colonization and facilitate access to eukaryotic cell-surface receptors by the cleavage of ECM proteins. Thus, serine proteases could be promising candidates for developing antimicrobials to reduce pneumococcal colonization and transmission.
The pathobiont Streptococcus pneumoniae causes life-threatening diseases, including pneumonia, sepsis, meningitis, or non-invasive infections such as otitis media. Serine proteases are enzymes that have been emerged during evolution as one of the most abundant and functionally diverse group of proteins in eukaryotic and prokaryotic organisms. S. pneumoniae expresses up to four extracellular serine proteases belonging to the category of trypsin-like or subtilisin-like family proteins: HtrA, SFP, PrtA, and CbpG. These serine proteases have recently received increasing attention because of their immunogenicity and pivotal role in the interaction with host proteins. This review is summarizing and focusing on the molecular and functional analysis of pneumococcal serine proteases, thereby discussing their contribution to pathogenesis.
Streptococcus pneumoniae has evolved versatile strategies to colonize the nasopharynx of humans. Colonization is facilitated by direct interactions with host cell receptors or via binding to components of the extracellular matrix. In addition, pneumococci hijack host-derived extracellular proteases such as the serine protease plasmin(ogen) for ECM and mucus degradation as well as colonization. S. pneumoniae expresses strain-dependent up to four serine proteases. In this study, we assessed the role of secreted or cell-bound serine proteases HtrA, PrtA, SFP, and CbpG, in adherence assays and in a mouse colonization model. We hypothesized that the redundancy of serine proteases compensates for the deficiency of a single enzyme. Therefore, double and triple mutants were generated in serotype 19F strain EF3030 and serotype 4 strain TIGR4. Strain EF3030 produces only three serine proteases and lacks the SFP encoding gene. In adherence studies using Detroit-562 epithelial cells, we demonstrated that both TIGR4Δcps and 19F mutants without serine proteases or expressing only CbpG, HtrA, or PrtA have a reduced ability to adhere to Detroit-562 cells. Consistent with these results, we show that the mutants of strain 19F, which preferentially colonizes mice, abrogate nasopharyngeal colonization in CD-1 mice after intranasal infection. The bacterial load in the nasopharynx was monitored for 14 days. Importantly, mutants showed significantly lower bacterial numbers in the nasopharynx two days after infection. Similarly, we detected a significantly reduced pneumococcal colonization on days 3, 7, and 14 post-inoculations. To assess the impact of pneumococcal serine proteases on acute infection, we infected mice intranasally with bioluminescent and invasive TIGR4 or isogenic triple mutants expressing only CbpG, HtrA, PrtA, or SFP. We imaged the acute lung infection in real-time and determined the survival of the mice. The TIGR4lux mutant expressing only PrtA showed a significant attenuation and was less virulent in the acute pneumonia model. In conclusion, our results showed that pneumococcal serine proteases contributed significantly to pneumococcal colonization but played only a minor role in pneumonia and invasive diseases. Because colonization is a prerequisite for invasive diseases and transmission, these enzymes could be promising candidates for the development of antimicrobials to reduce pneumococcal transmission.
Wadi Wurayah area is located in the north of Fujairah Emirates between the towns of Khor Bidiyah Fakkan and Oman on the Gulf Coast Line in Fujairah Emirates, United Arab Emirates. It lies within a priority World Wide Fund for Nature ( WWF) Global 200 Ecoregions ( ecoregion 127, Arabian Highland Woodlands and Shrublands ), a rich diversity of sheltering rare and endangered mountainous and freshwater habitats and species , and providing opportunities for the revival and sustenance of local livelihoods. However, as most of the United Arab Emirates and the region , the area is undergoing dramatic changes linked to economic diversification and promotion of tourism. The United Arab Emirates in 1999 approved the programmed of work from the UN convention of Biological Diversity ( CBD). This momentum must be used wants it or disappear. In a first move , the United Arab Emirates established the federal Environment Agency ( FEA) that produced the Environmental Law of 1999 with the role to encourage each to Emirates assess its land and coastal / marine resources, formulate plans for establishing protected areas , upgrade those that may already exist , and help implement the environment law. In early 2006, UAE created its first Ministry of Environment and Water ( MEW ), which was before the Ministry of Agriculture and Fisheries. Environmental issues and a greater role of the civil society are now higher on the agenda of the United Arab Emirates government , partner of the Emirates Wildlife Society ( EWS ), the World Wide Fund for Nature ( WWF) - UAE Project Office is the only international conservation NGOs operating in the UAE that plays a pioneering role in partnering with local- governmental institutions to establish win- win solutions. The United Arab Emirates is making tremendous efforts in diversification is the development of tourism. Too often tourism mass , With all of its negative environmental consequences is privileged. However, the more traditional Emirates are seeking alternatives that would preserve their environment and respect the traditional lifestyles of the local communities. This study aims to help a sustainable biosphere reserve integrating oneself local traditional and lifestyle with the conservation of biodiversity and habitat inimitable by providing a model of economical incentives unique to the region . In order to further the implementation of the Wadi Wurayah Biosphere Reserve, this study will: • Implement a set of carefully - targeted actions in Wadi Wurayah and its hinterland and therefore Fujairah Emirates. • Work to demonstrate the feasibility and viability of combining environmental protection in a sensitive area with the preservation of traditional activities. • Support the capacity building of key national and local authorities and selected partners in the Emirates of Fujairah and the UAE So that they have the awareness and skills to fully realize the aims of the study . To set out and develop options for sustainable natural resource management in the proposed Wurayah Biosphere Reserve , one of the UAE as examples of marginal dry lands , building on environmental information system was the best choice using Geographic information systems (GIS ) as a tool. This has been classified to there steps of work: Field Survey and Analysis Lab Office work. As a first step, this study used to survey this area in the light of the work done by the EWSWWF and the Fujairah Municipality, to evaluate the potential and the feasibility of the creation of a Biosphere Reserve. The traditional field survey has been carried out in three batches between January 2007 and January , 2009 for sample collection using specially tailored database forms that suit the properties and nature of the variables measured, and the database . Design The information obtained from field survey included the Landscape and their local classification and distribution , local habitats , water catchments areas , local rangeland systems and indigenous agro -ecological zones. This information in addition to the laboratory analysis has then be transformed into GIS format, and overlaid with the base maps of the study area in order to produce a georeferenced maps. Various types of maps required according the selected works related to area of study have been used as an input data for the GIS system An integrated management methodology / approach has been proposed associated with the plan of work throughout the forthcoming years. The plan of work is designed to be as consistent as possible with that of the concept of the UNESCO 's Man and Biosphere Program.
Background: Restorative treatment for children’s teeth is still an important aspect of dentistry. In the light of an only moderate caries decline in the primary dentition and a persistently low care index in Germany during the past years [DAJ 2010], there is still a demand for further work on recent patterns and outcomes of restorative treatments in primary teeth placed in everyday practices under the Germany National Health System. Objectives: The present study aimed firstly to describe the prevalence of caries and restorations in the primary teeth in Berlin and Germany from the representative Germany surveys [DAJ 2010], secondly, to describe the frequency and distribution of restorative treatment in primary teeth performed in everyday dental practice in Berlin including children age groups from 1- to 13-years of age, thirdly, to evaluate the outcomes of restorative treatment performed in everyday dental practices in these children and finally to compare results of the present study with data from the German National Health System [KZBV 2011] and randomized community data on the longevity of restorations in primary teeth in Denmark [Qvist et al. 2010a]. Material and Methodology: In the first part of present study data from representative German surveys [DAJ 2010] were interpreted to describe and compare the prevalence of caries and restorations in the primary teeth in Berlin and Germany. For the second and third parts data generated from German National Health System in Berlin (KZV-Berlin) on fillings done in everyday practices in primary teeth of 1- to 13-year-olds during 2010/2011 were collected. This data included: distribution of children with dental treatment regardless of the type of intervention provided, of children who received restorative treatments in primary teeth during dental care visits including total number of fillings per child, the number of filled tooth surfaces, retreatment with another filling, stainless steel crowns, pulp involvement and extractions after prior filling therapy. Information on the age of the original fillings at the time of retreatment was also included. The collected data then were entered into a data base for descriptive and analytical analysis. The results were compared with equivalent data from the German National Health System [KZBV 2011] and randomized community data from Denmark [Qvist et al. 2010a]. Results: Result showed a high similarity in patterns of caries and restorative treatment in primary teeth in Berlin and all of Germany as reported in the representative German surveys [DAJ 2010]. About of 84% of 1-13-year-olds insured in the German National Health System in Berlin received dental care during 2010/2011, with considerably lower rates in very young children. Fillings in primary teeth were performed in 31.17% of all children attending the dentist. Most restorations were placed in 5-8-year-olds. In 1-13-year-olds mostly just one filling was placed, more than five fillings were per child were recorded on average for very young age groups (1-4-year-olds). 55.60% of all fillings in primary teeth were two-surface restorations, whereas more than three-surface restorations comprised 6.17% of all fillings and they were performed most frequently in young children of 1-4-years of age. Retreatment to fillings in primary teeth was 7.66% of fillings placed in 1-13-year-olds. Most retreatments took place from 5 to 9 years of age with a peak in 6-year-olds. In 1-3-year-old children fillings showed shorter mean age at the time of retreatment compared to 7-year-olds and above. Retreatment of fillings in primary teeth by stainless steel crowns was very limited with only 5.16% of all retreatments and it was preferred in children from 3 to 7 years of age. The retreatment with pulp involvement was 11.27% of all retreatments. Extractions were almost as often as retreatment as another filling (ratio 4:5), but they were preferred in older children due to the course of exfoliation. Conclusions: Under the conditions of this retrospective study, the restorative treatment with fillings performed within the National Health System in primary teeth in Berlin was very successful with low rates of retreatment and the fillings shows comparable results to data on the longevity of restorations in primary teeth in Denmark. The study highlighted the need to a structured program for prevention in primary teeth, especially for very young children with high caries activity and possibly also different treatment structures with specialized dentists in this field who can perform oral rehabilitations with pulpotomies and stainless steel crowns.
Sealing ability of ProRoot MTA when placed as an apical barrier using three different techniques
(2013)
A one-visit apexification protocol with Mineral Trioxide Aggregate (MTA) can be seen as an alternative to the traditional treatment practices with calcium hydroxide. The aim of this study was to investigate the sealing ability of ProRoot MTA when placed as an apical barrier using three different techniques. Sixty freshly extracted single-rooted human teeth were decoronated and standardized to a root length of 15mm. The root segments were prepared with Gates Glidden burs (size 1-6) to simulate the clinical situation of an open apex and randomly assigned into 3 experimental groups of 20 samples each. 5mm MTA was placed by pluggers (Group 1) paper points (Group 2) or ultrasonic tips (Group 3). Radiographs were taken to verify the placement of the apical barriers. After obturation of all samples with warm gutta-percha (Obtura) and AH26 sealer, the coronal portion of all samples was sealed with Cavit. The root segments were then double coated with nail varnish except for the open apex and were exposed to methylene blue dye for 48 hours at room temperature. Afterwards, the samples were sectioned longitudinally and the extent of dye penetration was measured with a stereomicroscope. The mean depth of dye leakage for Group 1 was 1.34mm (±0.5 SD) Group 2 1.25mm (±0.4 SD) and Group 3 1.14mm (± 0.4 SD). Statistical analysis showed that there were no significant differences among the 3 experimental groups (0.178<p<0.552). In conclusion, ProRoot MTA has a similar sealing ability when placed as an apical barrier with pluggers, paper points or ultrasonic tips.
Background: This study aims to assess the role of ductoscopy for detecting intraductal anomalies in patients with nipple discharge in comparison to conventional tests and to find an effective combination of both approaches. Materials and Methods: Prior to duct excision, ductoscopy was performed in 97 women. Histologic and all other diagnostic results were compared. Sensitivity, specificity, and efficiency were calculated for all methods. These parameters were also calculated for all possible test combinations in 12 patients who had completed all tests. Results: Breast sonography reached the highest sensitivity (64.1%) and efficiency (64%); mammography had the highest specificity (100%). The sensitivity of ductoscopy was 53.2%, its specificity 60%, and its efficiency 55.1%. Among combinations of all methods, the combination ductoscopy + galactography was the most sensitive (80%). Mammography, magnetic resonance imaging, and ductoscopy were each 100% specific. Ductoscopy was the most efficient (75%) single method. Conclusion: Ductoscopy is a valuable test for diagnosing intraductal lesions in patients with nipple discharge. It is more efficient than conventional tests in patients undergoing all tests.
National oral health survey on refugees in Germany 2016/2017: caries and subsequent complications
(2020)
Objectives To assess oral health, caries prevalence, and subsequent complications among recently arrived refugees in Germany and to ompare these findings with the German resident population. Methods This multicenter cross-sectional study recruited 544 refugees aged 3–75+ years; they were examined at ten registration institutions in four federal states in Germany by two calibrated dentists. The refugees were screened for caries (dmft/DMFT) and its complications pufa/PUFA); this data was compared to the resident population via the presentative national oral health surveys). Results The deciduous dentition of the 3-year-old refugees had a mean dmft value of 2.62 ± 3.6 compared with 0.48 dmft in the German resident population, and caries increased to 5.22 ± 3.4 for 6–7-year-olds (Germany: 1.73 dmft). Few refugee children had naturally healthy teeth (7% in 6–7-year-olds, Germany: 56%). In the permanent dentition, the gap in caries prevalence between refugees and the German population decreased with age (35–44-year-olds: 10.55 ± 7.1 DMFT; Germany: 11.2), but refugees exhibited more caries defects (35–44-year-olds DT = 3.13 ± 3.0; Germany: 0.5). German residents had more restorations (35–44-year-olds FT = 4.21 ± 4.6). Regarding complications, the 6–7-year-olds exhibited the highest pufa index (0.86 ± 1.4) which decreased in adolescence (13–17-year-olds, 0.18 ± 0.6) and increased in adults (45–64-year-olds, 0.45 ± 0.8). Conclusion The refugees had high caries experience, often untreated caries teeth and more complications compared with the German resident population, especially in children. Closing this gap by extending preventive systems to the refugees would decrease future treatment needs. Clinical relevance European countries should be prepared for the higher dental treatment needs in recent refugees, especially in
children.